溶剂梯度双柱循环色谱在微量杂质分离制备中的应用

Application of Solvent Gradient Dual Column Cyclic Chromatography in the Separation and Preparation of Trace Impurities

杂质对于药物的疗效及安全性具有一定的负面作用,因此需要对其进行分离与提取以保证药物的临床安全性。研究采用了双柱循环色谱工艺,在此基础上引入了溶剂梯度对其进行谱带压缩,并将其应用到实际的药物关键杂质的分离当中。结果显示,在探究洗脱剂含水率对分离效果的影响实验中,相比于11%的洗脱剂含水率,13%的洗脱剂含水率的纯度、收率及产率分别提升了15.2%、7%、5.2%。同时,研究分析了溶剂梯度对分离效果的影响,结果显示,产品的纯度在溶剂梯度为1.5%时最高,为52.3%。此外,在探究循环周期对分离效果的影响实验中,循环周期为28.5 min的产品收率高达90.1%。说明引入了溶剂梯度的双柱循环色谱技术具有十分显著的优势以及很强的可行性,为药物微量杂质的分离提供了有效的技术支持。

Impurities have a certain negative impact on the efficacy and safety of drugs,so it is necessary to separate and extract them to ensure the clinical safety of drugs.The study adopts a dual column cyclic chromatography process,on this basis the solvent gradients are introduced for band compression and applied to the separation of key impurities in actual drugs.The results show that in the experiment of exploring the influence of the water content of the eluent on the separation effect,compared to the 11%water content of the eluent,the purity,yield,and productivity of the 13%water content of the eluent increases by 15.2%,7%and 5.2%,respectively.Meanwhile the study also analyzes the effect of solvent gradient on the separation efficiency,and the results show that the purity of the product is the highest which is 52.3%when the solvent gradient is 1.5%.In addition,in the experiment of exploring the impact of cycle time on the separation efficiency,the product yield with a cycle time of 28.5 min reaches 90.1%.The introduction of solvent gradient dual column cyclic chromatography technology has significant advantages and strong feasibility,which provides an effective technical support for the separation of trace impurities in drugs.